A goal of regenerative medicine is to produce a fully functional tissue or organ to replace one that has been damaged or destroyed by injury, disease, or aging. Currently, treatment of a full-thickness skin wound such as a deep burn or chronic ulcer represents a significant clinical challenge. Autologous skin grafts are considered to be the best treatment for such wounds but have multiple drawbacks and limitations. For instance, if the defect area exceeds fifty percent of total body surface area, it is often not practical to use autologous skin grafting due to shortage of donor sites. Furthermore, an additional wound is created at the donor site. Traditional skin grafts, once healed, can provide a barrier function, but generally do not contain sweat glands, hair follicles, or fully developed sub-cutis.
To address the limitation of donor sites, tissue-engineered skin has been developed using in vitro cultured cells. Such skin equivalents, or skin substitutes, have been used to repair cutaneous wounds due to trauma, burn, surgery, or chronic ulceration. The application of skin substitute as an alternative to autologous skin grafts has had limited long-term clinical success because substitutes lack neither normal dermal structure. The substitutes also lack the structures critical for normal functioning skin such as sweat glands, hair follicles, and sub-cutis.
There is a need in the art for a method to culture human cells while retaining and enhancing their ability to completely regenerate a full-thickness human skin organ that can interact with other cells and form functioning skin structures such as sweat glands, nerves, hair follicles, blood vessel, and adipose. There are unmet clinical needs for therapies to treat deep wounds, burns, chronic wounds, and so forth while avoiding scarring.